Weekly basal insulin plus semaglutide shows benefit in type 2 diabetes

A 40-week clinical trial found that a once-weekly injection combining basal insulin icodec with semaglutide, called IcoSema, lowered blood sugar and body weight more than a commonly used daily insulin, glargine U100, in adults with type 2 diabetes^[1]. The study, known as COMBINE 4, also found fewer low-blood-sugar events with the combination shot^[1]. The results were published in The Lancet Diabetes & Endocrinology and reported by Medscape Medical News on September 10, 2026^[1].

The trial enrolled 485 adults with type 2 diabetes who were already taking oral diabetes medications but had never used insulin or a GLP-1 receptor agonist drug^[1]. Researchers randomly assigned 243 people to the weekly IcoSema shot and 242 to daily glargine U100^[1]. More than 90% of participants in both groups finished the 40-week study^[1]. Most participants, 87%, were also taking metformin, and about a third were on SGLT2 inhibitor drugs^[1].

By week 40, average A1c, a measure of long-term blood sugar control, dropped from 9.57% to 6.22% in the IcoSema group, compared with a drop from 9.50% to 7.10% in the glargine group, a difference researchers called statistically significant^[1]. Body weight fell by about 1.7 pounds on average with IcoSema, while people on glargine gained about 8.4 pounds on average^[1]. Significant low-blood-sugar episodes occurred in 9% of the IcoSema group versus 22% of the glargine group, and severe hypoglycemia was also less frequent, with three episodes in two IcoSema patients compared with six episodes in five glargine patients^[1]. But gastrointestinal side effects, such as nausea, were more common with IcoSema, affecting 56% of participants compared with 21% on glargine, and led four people to stop the drug, compared with none in the glargine group^[1].

Earlier related trials, called COMBINE 1 through 3, had already tested IcoSema against insulin icodec alone, semaglutide alone, and a daily glargine-plus-mealtime-insulin regimen, according to the report^[1].

Why it matters for patients

For people with type 2 diabetes who need to add insulin to oral medications, this study suggests a once-weekly shot combining insulin and semaglutide could lower blood sugar with less risk of weight gain and low-blood-sugar episodes than a standard daily insulin, according to the researchers^[1]. That could mean fewer injections for people who already take both a GLP-1 drug and insulin. Study author Linong Ji, a diabetes specialist at Peking University, wrote that the drug combination "might be a feasible treatment option" for people starting insulin, and could reduce "injection burden" while easing concerns about weight gain and low blood sugar^[1].

However, the combination is not available in the United States. It is approved under the brand name Kyinsu in the European Union, China, Japan, South Korea, and some other countries, but Novo Nordisk, the drug's maker, has not yet filed for approval in the US^[1]. A company spokesperson told Medscape that Novo Nordisk is still deciding whether and when to file^[1]. The gastrointestinal side effects seen in the trial, along with the higher discontinuation rate compared with glargine, are also relevant for anyone weighing the tradeoffs of this regimen once it becomes available^[1].

What happens next

Insulin icodec alone, sold as Awiqli, won FDA approval for type 2 diabetes in March 2026, after an earlier rejection tied to hypoglycemia concerns when the company sought approval for both type 1 and type 2 diabetes^[1]. The combination product IcoSema has not been filed with the FDA, and no US approval timeline has been announced^[1]. The study was funded by Novo Nordisk, and the findings have not changed any existing drug labeling^[1].